From Wikipedia, the free encyclopedia
Jump to navigation Jump to search

Lq2 is a component of the venom of the scorpion Leiurus quinquestriatus. It blocks various potassium channels, among others the inward-rectifier potassium ion channel ROMK1.[1]


Alternative names[edit]

Lq2 is also known as Potassium channel toxin alpha-KTx 1.2, Charybdotoxin-2, ChTX-Lq2, ChTx-d, Toxin 18-2 or Lqh 18-2.


The name Lq2 refers to the name of the animal species in which the toxin can be found.[2] Lq2 can be found in the scorpion Leiurus quinquestriatus (Lq).[3][4] Lq2 is structurally similar to Lq1, which had been found previously and which is also a potassium channel blocker.


Lq2 is a component of the venom of the scorpion Leiurus quinquestriatus, known under various names, for example the deathstalker, the Israeli desert scorpion or the yellow scorpion.


Lq2 is a small peptide of 37 amino acids. Lq2 contains the classical scorpion toxin alpha-beta scaffold and is structurally similar to the neurotoxin Charybdotoxin (CTX).[5] Lq2 consists of an α-helix and a β-sheet, connected by an αβ3 loop containing disulfide bridges. The proteins three-dimensional structure has been reconstructed using nuclear magnetic resonance techniques.[5]


Lq2 interacts with all three types of potassium channels:[6] the voltage-activated, the Ca2+- activated and the inward-rectifier potassium channels.[7] The unique trait of Lq2 is its high affinity for certain inward-rectifier potassium ion channels, especially the Renal Outer Medullary Potassium channel ROMK1. This ion channel contributes to the regulation of the resting membrane potential.

Mode of action[edit]

Since all potassium channels share the same ion conducting outer pore structure, Lq2 binds to all three potassium channel types. Lq2 interacts with the T-X-X-T-X-GT-X-X-T-X-GY/F-Gt K+-selective section within the pore-forming region (P-region) of the ROMK1 ion channel. It blocks the channel, binding in a 1:1 stoichiometric ratio with its β-sheet.[8]

Therapeutic use[edit]

Potential use of Lq2 is mainly in cardiovascular diseases.[3]


  1. ^ Kubo Y, Adelman JP, Clapham DE, et al. (December 2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID 16382105.
  2. ^ Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T (February 2007). "Voltage-gated ion channels and gating modifier toxins". Toxicon. 49 (2): 124–41. doi:10.1016/j.toxicon.2006.09.022. PMID 17239913.
  3. ^ a b Cui M, Shen J, Briggs JM, et al. (April 2001). "Brownian dynamics simulations of interaction between scorpion toxin Lq2 and potassium ion channel". Biophysical Journal. 80 (4): 1659–69. doi:10.1016/S0006-3495(01)76138-3. PMC 1301357. PMID 11259281.
  4. ^ MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT (April 1998). "Structural conservation in prokaryotic and eukaryotic potassium channels". Science. 280 (5360): 106–9. doi:10.1126/science.280.5360.106. PMID 9525854.
  5. ^ a b Renisio JG, Lu Z, Blanc E, et al. (March 1999). "Solution structure of potassium channel-inhibiting scorpion toxin Lq2". Proteins. 34 (4): 417–26. doi:10.1002/(SICI)1097-0134(19990301)34:4<417::AID-PROT1>3.0.CO;2-R. PMID 10081954.
  6. ^ Isomoto S, Kondo C, Kurachi Y (February 1997). "Inwardly rectifying potassium channels: their molecular heterogeneity and function". The Japanese Journal of Physiology. 47 (1): 11–39. doi:10.2170/jjphysiol.47.11. PMID 9159640.
  7. ^ Neusch C, Weishaupt JH, Bähr M (February 2003). "Kir channels in the CNS: emerging new roles and implications for neurological diseases". Cell and Tissue Research. 311 (2): 131–8. doi:10.1007/s00441-002-0669-x. PMID 12596033.
  8. ^ Lu Z, MacKinnon R (June 1997). "Purification, characterization, and synthesis of an inward-rectifier K+ channel inhibitor from scorpion venom". Biochemistry. 36 (23): 6936–40. doi:10.1021/bi9702849. PMID 9188688.